The goal of this three-year proposal is to develop and evaluate a new technique for detection and quantitation of early atherosclerosis of coronary arteries before obvious, discrete, lumenal stenoses occur. We propose to use multislice fast x-ray CT to provide the direct measurement of coronary artery lumen cross-sectional area needed to establish the presence of diffuse lumenal narrowing. The novel aspect of this proposal is that the individualized baseline physiological arterial lumen cross- sectional area (against which the measured pathological diffuse lumenal narrowing can be compared) will be derived from the recently demonstrated relationship between coronary artery lumenal cross-sectional area and the branching geometry of the upstream and downstream coronary arterial tree. This branching geometry will be characterized by cumulative segment length of the artery, from aortic origin to the arterial segment's cross section of interest, and by the mass of myocardium perfused by the artery downstream to the cross section of interest. First we propose to establish how precise and reproducible an estimate of physiological coronary arterial lumen cross-sectional areas can be made in a range of patient types with or without diseases of the myocardium. This will be achieved in Aim I using cadaver hearts with postmortem measurements used as the standard against which the CT based measurements will be compared. Second, in order to determine if this approach can be applied clinically we will modify in Aim II (via software and/or collimation) an electron- beam CT scanner to provide the 3D imaging resolution necessary, within one 6 second breathold period, to achieve the clinical aspect of our study objectives. Finally, in Aim III we will use Technetium 99m MIBI scan data, performed in patients with acute arterial occlusion who are subsequently treated with adenosine and thrombolysis, to provide an independent, validated estimate of that myocardial mass perfused by the temporarily occluded vessel segment. We will compare the CT-based estimate of the perfused mass against the Tc-99m MIBI-based value. If successful, this aspect of the CT-based analysis of the coronary arterial tree will provide the basis for an independent estimate of normal vessel cross-sectional area. The significance of a successful outcome of this proposal is that patients with high risk factors for coronary atherosclerosis could be quantitatively evaluated before symptoms of coronary stenosis are likely to occur. This would be achieved by a CT scan during a single breathold following a single intravenous injection of contrast agent.